Project Abstract The Keyence BZ-X800E All-in-One fluorescent microscope is a unique instrument that provides multi-color fluorescent imaging, 3D image rendering and measurement localization, live cell and time-lapse video generation, automated multi-image collection, and real-time image stitching and image analysis. Thus, the Keyence microscope will be a crucial instrument for VAWNYHS investigators, and the unique features will have immediate benefits for VA-funded projects below. Dr. Troen?s work investigates musculoskeletal aging, frailty, and functional capacity in older veterans. Dr. Troen is conducting both human and animal studies to explore the benefits of high intensity interval training (HIIT) and nutritional supplements on skeletal muscle and bone morphology and function during aging. The Keyence will allow more precise assessments of muscle fibers in a fraction of the time of the current methodology. The Keyence will also be able to generate time-lapse live cell imaging video to observe the formation and activity of bone resorbing osteoclasts, capture the impacts of reagent interventions, and facilitate analysis of bones from experimental animals. Dr. Fliesler?s projects investigate the underlying mechanism of progressive retinal degeneration and visual dysfunction associated with blast overpressure-induced polytrauma, and the impact of novel antioxidants as therapeutic agents to prevent, minimize, or slow the progression of the pathological processes. The Keyence microscope will afford quantitative assessment of histological damage and biomarkers of oxidative stress, cell death, and gliosis. Dr. Sullivan?s study investigates the development of post-transcriptional gene silencing agents such as ribozymes (catalytic RNAs) as candidate therapeutics for orphan retinal degenerations (e.g. retinitis pigmentosa) and common age-related macular degeneration (AMD). The Keyence will provide dramatic new methodologies to observe cellular RNA trafficking and investigate the kinetics and steady-state outcomes of catalytic RNA (ribozyme) therapeutics. Dr. Canty?s study investigates dynamic remodeling during sudden cardiac arrest and cardiac stem cell mediated repair. The Keyence will facilitate characterization of specific hematopoietic subtypes and macrophage polarization and enable characterization of stems in culture to better understand how adult stem cells stimulate endogenous myocyte proliferation. Dr. Feng?s study seeks to understand how mutations of parkin cause the selective degeneration of human nigral dopaminergic neurons and the ensuing Parkinson?s disease. The Keyence will allow the ability to monitor morphological changes and enable imaging of iPSC-derived midbrain DA neurons, to identify impacts of parkin mutations as a model of idiopathic Parkinson?s disease. Dr. Lang?s research seeks to determine the functional role of exosomes in stem cell-mediated cardiac repair. The Keyence microscope will enhance this work by facilitating extremely high resolution immunohistological analysis of murine cardiac tissue following myocardial infarction and evaluating the potential of exosome-based therapy to ameliorate damaged tissues. The range of applications provided by the Keyence BZ-X800E microscope will greatly facilitate our understanding of the underlying acute and chronic processes that result in physiological dysfunction, disease, and health decline. Further, it will be an essential tool for the VAWNYHS researchers to develop effective interventions to minimize the severity, delay the onset, or arrest the progression of frailty and ultimately improve the quality of life in the veteran population.